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首页> 外文期刊>British Journal of Haematology >Methyljasmonate displays in vitro and in vivo activity against multiple myeloma cells
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Methyljasmonate displays in vitro and in vivo activity against multiple myeloma cells

机译：茉莉酸甲酯显示出对多种骨髓瘤细胞的体外和体内活性

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Jasmonates, plant stress hormones, have been demonstrated to be effective in killing various types of cancer cells. We therefore tested if methyljasmonate (MJ) has activity against multiple myeloma (MM) in vitro and in vivo. MM cell lines and primary MM tumour cells responded to MJ in vitro at concentrations that did not significantly affect normal haematopoietic cells, without stroma-mediated resistance. Brief MJ exposures of MM cells caused release of Hexokinase 2 (HK2) from mitochondria, rapid ATP depletion, perturbation of major intracellular signalling pathways, and ensuing mainly apoptotic cell death. Sensitivity to MJ correlated with lower cellular glucose consumption and lactate production, as well as lower intracellular protein levels of HK2, phosphorylated Voltage-dependent anion channel 2/3 (pVDAC2/3) and Aldo-keto reductase family 1 member C1 (AKR1C1), which represent potential biomarkers of responsiveness to MJ treatment, especially as AKR1C1 transcript levels also correlate with clinical outcome in bortezomib- or dexamethasone-treated MM patients. Interestingly, MJ synergized with bortezomib in vitro and prolonged survival of immunocompromised mice harbouring diffuse lesions of MM.1S cells compared to vehicle-treated mice (P = 0·0046). These studies indicate that jasmonates represent a new, promising strategy to treat MM.
机译：茉莉酸盐，植物胁迫激素，已被证明可有效杀死各种类型的癌细胞。因此，我们在体外和体内测试了茉莉酸甲酯（MJ）是否对多发性骨髓瘤（MM）具有活性。在没有基质介导的抗性的情况下，MM细胞系和原发性MM肿瘤细胞在体外对MJ的反应浓度不会显着影响正常的造血细胞。 MM细胞的短暂MJ暴露导致线粒体释放Hexokinase 2（HK2），ATP迅速耗竭，干扰了主要的细胞内信号通路，并随后导致凋亡性细胞死亡。对MJ的敏感性与较低的细胞葡萄糖消耗和乳酸产生以及较低的HK2，磷酸化电压依赖性阴离子通道2/3（pVDAC2 / 3）和Aldo-酮基还原酶家族1成员C1（AKR1C1）的细胞内蛋白质水平相关，代表了对MJ治疗反应的潜在生物标志物，尤其是AKR1C1转录水平也与硼替佐米或地塞米松治疗的MM患者的临床结局相关。有趣的是，与媒介物治疗的小鼠相比，MJ在体外与硼替佐米协同作用，并延长了带有MM.1S细胞弥散性病变的免疫受损小鼠的存活期（P = 0·0046）。这些研究表明，茉莉酸酯代表了一种新的，有前途的治疗MM的策略。

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